Neovascularization refers generally to the formation of functional vascular (e.g., microvascular) networks. The formation may involve proliferation of blood vessels in tissue not normally containing blood vessels, or of blood vessels of a different type than found in the neovascularized tissue under normal physiological conditions. For example, choroidal neovascularization (CNV) involves the invasion of new blood vessels at the choroid. CNV can involve abnormalities in Bruch's membrane forming the innermost layer of the choroid. The resulting neovascular tissue can cause physical separation of the laminar structure of the retina and destruction of normal retinal tissue in turn causing leakage, bleeding, and blindness. Accordingly, CNV is associated with a variety of diseases of the eye including age-related macular degeneration (AMD). For example, in the so-called “wet” form of AMD, CNV develops in the choriocapillaris and subretinal space, disrupting the retinal pigment epithelium (RPE) which results in significant loss of the central vision. See e.g., Green, 1999, Mol. Vis. 5:27. Indeed, AMD is a leading cause of blindness in older populations of developed countries. See e.g., Resnikoff et al., 2004, Bull. World Health Organ. 82:844-851.
Occlusion of retinal vessels leading to ischemia and/or hypoxia is common in CNV. See e.g., Michaelson I., 1948, Trans Ophthalmol Soc UK. 68:137-180; Ashton N., 1957, Am J Ophthalmol. 44:7-17; 6. Shimizu K, et al., 1981, Ophthalmology 88:601-612. Extensive evidence on the involvement of Vascular Endothelial Growth Factor (VEGF) has been provided. For example, VEGF is upregulated in hypoxia, and levels of VEGF are increased with ischemic retinopathy. See e.g., Shweiki D, et al., 1992, Nature 359:843-845; Plate K H, et al., 1992, Nature 359:845-848; Forsythe J A, et al., 1996, Mol Cell Biol. 16:4604-4613; Adamis A P, et al., 1994, Am J Ophthalmol 118:445-450; 12. Aiello L P, et al., 1994, N Engl J Med. 331:1480-1487; Malecaze F, et al., 1992, Arch Ophthalmol. 112:1476-1482; Pe'er J, et al., 1995, Lab Invest. 72:638-645; Miller J W, et al., 1994, Am J Pathol. 145:574-584; Pierce E A, et al., 1995, Proc Natl Acad Sci USA. 92:905-909. Indeed, increased expression of VEGF in retinal photoreceptors of transgenic mice stimulates neovascularization within the retina, and VEGF antagonists partially inhibit retinal neovascularization in animal models. See e.g., Okamoto N, et al. 1997, Am J Pathol. 151:281-291; Tobe T, et al., 1998, Invest Ophthalmol Vis Sci. 39:180-188; Aiello L P, et al., 1995, Proc Natl Acad Sci USA. 92:10457-104611 Robinson G S, et al., 1996, Proc Natl Acad Sci USA. 93:4851-4856; Adamis A P, et al., 1996, Arch Ophthalmol. 114:66-71. Moreover, overexpression of VEGF in the subretinal space results in neovascularization of the choroidal membranes and death of the overlying photoreceptor cells. See e.g., Spilsbury, K., et al., 2000, Am. J. Pathology 157:135-144.
Accordingly, there is a need to decrease neovascularization (e.g., CNV) in subjects in need thereof. There are provided herein methods and compounds useful, inter alia, to decrease neovascularization.